Insights into the Management of Chronic Hepatitis in Children—From Oxidative Stress to Antioxidant Therapy
Abstract
:1. Introduction
2. Viral Chronic Hepatitis and Oxidative Stress
2.1. Hepatitis C Virus and Oxidative Stress
2.2. Hepatitis B Virus and Oxidative Stress
2.3. Chronic Hepatitis C Virus vs. Chronic Hepatitis B Virus
3. Other Chronic Hepatitis
3.1. Wilson Disease (WD)
3.2. Autoimmune Hepatitis
4. Treatments and Antioxidants Used in Chronic Viral Hepatitis
5. Conclusions
Author Contributions
Funding
Institutional Review Board Statement
Informed Consent Statement
Data Availability Statement
Conflicts of Interest
References
- Le Gal, K.; Schmidt, E.E.; Sayin, V.I. Cellular Redox Homeostasis. Antioxidants 2021, 10, 1377. [Google Scholar] [CrossRef] [PubMed]
- Averill-Bates, D. Reactive oxygen species and cell signaling. Review. Biochim. Biophys. Acta Mol. Cell Res. 2024, 1871, 119573. [Google Scholar] [CrossRef] [PubMed]
- Liu, Y.; Wu, Q.; Zhang, F.; Qin, X. Antioxidants-related nuclear factor erythroid 2-related factor 2 gene variants associated with HBV-related liver disease. Cancer Cell Int. 2023, 23, 72. [Google Scholar] [CrossRef] [PubMed]
- Allameh, A.; Niayesh-Mehr, R.; Aliarab, A.; Sebastiani, G.; Pantopoulos, K. Oxidative Stress in Liver Pathophysiology and Disease. Antioxidants 2023, 12, 1653. [Google Scholar] [CrossRef] [PubMed]
- Luangmonkong, T.; Suriguga, S.; Mutsaers, H.A.M.; Groothuis, G.M.M.; Olinga, P.; Boersema, M. Targeting Oxidative Stress for the Treatment of Liver Fibrosis. Rev. Physiol. Biochem. Pharmacol. 2018, 175, 71–102. [Google Scholar] [CrossRef] [PubMed]
- Rauf, A.; Khalil, A.A.; Awadallah, S.; Khan, S.A.; Abu-Izneid, T.; Kamran, M.; Hemeg, H.A.; Mubarak, M.S.; Khalid, A.; Wilairatana, P. Reactive oxygen species in biological systems: Pathways, associated diseases, and potential inhibitors—A review. Food Sci. Nutr. 2024, 12, 675–693. [Google Scholar] [CrossRef] [PubMed]
- Ighodaro, O.M.; Akinloye, O.A. First line defence antioxidants-superoxide dismutase (SOD), catalase (CAT) and glutathione peroxidase (GPX): Their fundamental role in the entire antioxidant defence grid. Alex. J. Med. 2018, 54, 287–293. [Google Scholar] [CrossRef]
- Zelber-Sagi, S.; Ivancovsky-Wajcman, D.; Fliss-Isakov, N.; Hahn, M.; Webb, M.; Shibolet, O.; Kariv, R.; Tirosh, O. Serum Malondialdehyde is Associated with Non-Alcoholic Fatty Liver and Related Liver Damage Differentially in Men and Women. Antioxidants 2020, 9, 578. [Google Scholar] [CrossRef]
- Li, S.; Tan, H.-Y.; Wang, N.; Zhang, Z.-J.; Lao, L.; Wong, C.-W.; Feng, Y. The Role of Oxidative Stress and Antioxidants in Liver Diseases. Int. J. Mol. Sci. 2015, 16, 26087–26124. [Google Scholar] [CrossRef]
- Gungor, S.; Köylü, A.A.; Saglam, S.; Neselioglu, S.; Erel, Ö.; Acıpayam, C. Effects of Oxidant-Antioxidant and Vitamin D Levels on Clinical and Laboratory Data in Children with Fatty Liver Disease. Cureus 2020, 12, e11849. [Google Scholar] [CrossRef]
- Zou, Y.-G.; Wang, H.; Li, W.-W.; Dai, D.-L. Challenges in pediatric inherited/metabolic liver disease: Focus on the disease spectrum, diagnosis and management of relatively common disorders. World J. Gastroenterol. 2023, 29, 2114–2126. [Google Scholar] [CrossRef] [PubMed]
- Abdelhamid, D.H.; Ahmed, M.D.H.A.L.B.; Talaat, M.A.S.H.I.M. Vitamin D Level in Pediatric Autoimmune Hepatitis: Relation to Features and Response to Therapy. Med. J. Cairo Univ. 2022, 90, 2653–2662. [Google Scholar] [CrossRef]
- Đorđević, V.; Đorđević, D.S.; Kocić, B.; Dinić, M.; Sokolović, D.; Stanković, J.P. The Impact of Hepatitis C Virus Genotypes on Oxidative Stress Markers and Catalase Activity. Oxidative Med. Cell. Longev. 2021, 2021, 6676057. [Google Scholar] [CrossRef] [PubMed]
- Méndez-Sánchez, N.; Córdova-Gallardo, J.; Barranco-Fragoso, B.; Eslam, M. Hepatic Dendritic Cells in the Development and Progression of Metabolic Steatohepatitis. Front. Immunol. 2021, 12, 641240. [Google Scholar] [CrossRef] [PubMed]
- Lazarus, J.V.; Picchio, C.A.; Colombo, M. Hepatocellular Carcinoma Prevention in the Era of Hepatitis C Elimination. Int. J. Mol. Sci. 2023, 24, 14404. [Google Scholar] [CrossRef] [PubMed]
- Abdalla, M.Y.; Ahmad, I.M.; Spitz, D.R.; Schmidt, W.N.; Britigan, B.E. Hepatitis C virus-core and non structural proteins lead to different effects on cellular antioxidant defenses. J. Med. Virol. 2005, 76, 489–497. [Google Scholar] [CrossRef] [PubMed]
- Afridi, S.; Naeem, M.; Hussain, A.; Kakar, N.; Babar, M.E.; Ahmad, J. Prevalence of hepatitis C virus (HCV) genotypes in Balochistan. Mol. Biol. Rep. 2009, 36, 1511–1514. [Google Scholar] [CrossRef]
- Jain, S.K.; Pemberton, P.W.; Smith, A.; McMahon, R.F.; Burrows, P.C.; Aboutwerat, A.; Warnes, T.W. Oxidative stress in chronic hepatitis C: Not just a feature of late stage disease. J. Hepatol. 2002, 36, 805–811. [Google Scholar] [CrossRef]
- Arauz, J.; Ramos-Tovar, E.; Muriel, P. Redox state and methods to evaluate oxidative stress in liver damage: From bench to bedside. Ann. Hepatol. 2016, 15, 160–173. [Google Scholar]
- Forman, H.J.; Fukuto, J.M.; Miller, T.; Zhang, H.; Rinna, A.; Levy, S. The chemistry of cell signaling by reactive oxygen and nitrogen species and 4-hydroxynonenal. Arch. Biochem. Biophys. 2008, 477, 183–195. [Google Scholar] [CrossRef]
- Tell, G.; Vascotto, C.; Tiribelli, C. Alterations in the redox state and liver damage: Hints from the EASL Basic School of Hepatology. J. Hepatol. 2013, 58, 365–374. [Google Scholar] [CrossRef] [PubMed]
- Ciragil, P.; Kurutas, E.B.; Kokoglu, O.F.; Aral, M. Oxidative Stress in Patients with Chronic Hepatitis B And C. Med. J. Trak. Univ. 2010, 28, 300–303. [Google Scholar] [CrossRef]
- De Andrade, K.Q.; Moura, F.A.; Dos Santos, J.M.; De Araújo, O.R.P.; De Farias Santos, J.C.; Goulart, M.O.F. Oxidative Stress and Inflammation in Hepatic Diseases: Therapeutic Possibilities of N-Acetylcysteine. Int. J. Mol. Sci. 2015, 16, 30269–30308. [Google Scholar] [CrossRef]
- Marí, M.; Colell, A.; Morales, A.; von Montfort, C.; Garcia-Ruiz, C.; Fernández-Checa, J.C. Redox control of liver function in health and disease. Antioxid. Redox Signal 2010, 12, 1295–1331. [Google Scholar] [CrossRef] [PubMed]
- Simula, M.P.; De Re, V. Hepatitis C virus-induced oxidative stress and mitochondrial dysfunction: A focus on recent advances in proteomics. Proteom. Clin. Appl. 2010, 4, 782–793. [Google Scholar] [CrossRef]
- Waris, G.; Huh, K.W.; Siddiqui, A. Mitochondrially associated hepatitis B virus X protein constitutively activates transcription factors STAT-3 and NF-kappa B via oxidative stress. Mol. Cell Biol. 2001, 21, 7721–7730. [Google Scholar] [CrossRef]
- Almaeen, A.; Alduraywish, A.; Mobasher, M.; Almadhi, O.; Nafeh, H.; El-Metwally, T. Oxidative stress, immunological and cellular hypoxia biomarkers in hepatitis C treatment-naïve and cirrhotic patients. Arch. Med. Sci. 2020, 17, 368–375. [Google Scholar] [CrossRef]
- Ivanov, A.V.; Bartosch, B.; Smirnova, O.A.; Isaguliants, M.G.; Kochetkov, S.N. HCV and oxidative stress in the liver. Viruses 2013, 5, 439–469. [Google Scholar] [CrossRef]
- Khedr, M.A.; El-Araby, H.A.; Konsowa, H.A.-S.; Sokar, S.S.; Mahmoud, M.F.; Adawy, N.M.; Zakaria, H.M. Glutathione peroxidase and malondialdehyde in children with chronic hepatitis C. Clin. Exp. Hepatol. 2019, 5, 81–87. [Google Scholar] [CrossRef]
- Toprak, G.; Sabancilar, I.; Özcan, N.; Alkan, H. Total Oxidant Status (TOS), Total Antioxidant Status (TAS), Ferritin and Vitamin D Levels in Patients with Chronic Hepatitis C. Microbiol. Infect. Dis. 2020, 4, 1–4. [Google Scholar] [CrossRef]
- Cai, J.; Hu, M.; Chen, Z.; Ling, Z. The roles and mechanisms of hypoxia in liver fibrosis. J. Transl. Med. 2021, 19, 186. [Google Scholar] [CrossRef]
- Monem, M.S.A.; Farid, S.F.; Abbassi, M.M.; Youssry, I.; Andraues, N.G.; Hassany, M.; Selim, Y.M.M.; El-Sayed, M.H. The potential hepatoprotective effect of metformin in hepatitis C virus-infected adolescent patients with beta thalassemia major: Randomised clinical trial. Int. J. Clin. Pract. 2021, 75, e14104. [Google Scholar] [CrossRef] [PubMed]
- Vuppalanchi, R.; Ghabril, M.; Chalasani, N.; Juluri, R.; Bell, L.N.; Kamendulis, L.; Klaunig, J.E.; Saxena, R.; Agarwal, D.; Johnson, M.S. Oxidative stress in chronic liver disease: Relationship between peripheral and hepatic measurements. Am. J. Med. Sci. 2011, 342, 314–317. [Google Scholar] [CrossRef] [PubMed]
- Ogunnaike, M.; Das, S.; Raut, S.S.; Sultana, A.; Nayan, M.U.; Ganesan, M.; Edagwa, B.J.; Osna, N.A.; Poluektova, L.Y. Chronic Hepatitis B Infection: New Approaches towards Cure. Biomolecules 2023, 13, 1208. [Google Scholar] [CrossRef] [PubMed]
- Approved Hepatitis B Drugs for Children (United States). Available online: https://www.hepb.org/treatment-and-management/treatment/approved-drugs-for-children/ (accessed on 24 January 2024).
- FDA Approves Tenofovir Alafenamide for Chronic Hepatitis B Virus in Pediatric Patients. Available online: https://www.pharmacytimes.com/view/fda-approves-tenofovir-alafenamide-for-chronic-hepatitis-b-virus-in-pediatric-patients (accessed on 24 January 2024).
- Yip, T.C.-F.; Wong, V.W.-S.; Chan, H.L.-Y.; Tse, Y.-K.; Lui, G.C.-Y.; Wong, G.L.-H. Tenofovir is associated with lower risk of hepatocellular carcinoma than entecavir in patients with chronic HBV infection in China. Gastroenterology 2020, 158, 215–225.e6. [Google Scholar] [CrossRef] [PubMed]
- Zhao, J.; Fan, Y.-C.; Sun, F.-K.; Zhao, Z.-H.; Wang, L.-Y.; Hu, L.-H.; Yin, Y.-P.; Li, T.; Gao, S.; Wang, K. Peripheral type I interferon receptor correlated with oxidative stress in chronic hepatitis B virus infection. J. Interf. Cytokine Res. 2013, 33, 405–414. [Google Scholar] [CrossRef] [PubMed]
- Şen, V.; Uluca, U.; Ece, A.; Kaplan, I.; Bozkurt, F.; Aktar, F.; Bağlı, S.; Tekin, R. Serum prolidase activity and oxidant–Antioxidant status in children with chronic hepatitis B virus infection. Ital. J. Pediatr. 2014, 40, 95. [Google Scholar] [CrossRef] [PubMed]
- Mahdy, K.; Shaheed, A.A.; Khadr, M.; El Shamy, K. Antioxidant status and lipid peroxidation activity in evaluating hepatocellular damage in children. East. Mediterr. Health J. 2009, 15, 842–852. [Google Scholar] [CrossRef] [PubMed]
- Acar, A.; Görenek, L.; Aydin, A.; Eyigün, C.P.; Eken, A.; Sayal, A.; Pahsa, A. Investigation of oxidative stress and antioxidant defense in patients with hepatitis B virus infection and the effect of interferon-alpha plus lamivudine combination therapy on oxidative stress. Mikrobiyol. Bul. 2009, 43, 411–423. [Google Scholar] [PubMed]
- Jiang, S.; Wang, J.; Zhang, Z.; Zhan, J.; Xue, R.; Qiu, Y.; Zhu, L.; Zhang, S.; Pan, Y.; Yan, X.; et al. Development and Validation of a Nomogram to Predict Significant Liver Inflammation in Patients with Chronic Hepatitis B. Infect. Drug Resist. 2023, 16, 5065–5075. [Google Scholar] [CrossRef]
- Severi, T.; Ying, C.; Vermeesch, J.R.; Cassiman, D.; Cnops, L.; Verslype, C.; Fevery, J.; Arckens, L.; Neyts, J.; van Pelt, J.F. Hepatitis B virus replication causes oxidative stress in HepAD38 liver cells. Mol. Cell. Biochem. 2006, 290, 79–85. [Google Scholar] [CrossRef]
- Ishizaka, N.; Ishizaka, Y.; Takahashi, E.; Toda, E.-I.; Hashimoto, H.; Ohno, M.; Nagai, R.; Yamakado, M. Increased prevalence of carotid atherosclerosis in hepatitis B virus carriers. Circulation 2002, 105, 1028–1030. [Google Scholar] [CrossRef]
- Abel, S.; De Kock, M.; van Schalkwyk, D.; Swanevelder, S.; Kew, M.; Gelderblom, W. Altered lipid profile, oxidative status and hepatitis B virus interactions in human hepatocellular carcinoma. Prostaglandins, Leukot. Essent. Fat. Acids 2009, 81, 391–399. [Google Scholar] [CrossRef] [PubMed]
- Thanan, R.; Oikawa, S.; Hiraku, Y.; Ohnishi, S.; Ma, N.; Pinlaor, S.; Yongvanit, P.; Kawanishi, S.; Murata, M. Oxidative stress and its significant roles in neurodegenerative diseases and cancer. Int. J. Mol. Sci. 2014, 16, 193–217. [Google Scholar] [CrossRef]
- Popadiuk, S.; Liberek, A.; Korzon, M.; Renke, J.; Woźniak, M. Free radical reactions and activity of antioxidant barrier in children with chronic hepatitis B. Med. Wieku Rozwoj. 2004, 8 Pt 2, 395–402. [Google Scholar]
- Wang, J.-H.; Lee, S.-B.; Lee, D.-S.; Son, C.-G. Total Antioxidant Capacity in HBV Carriers, a Promising Biomarker for Evaluating Hepatic Fibrosis: A Pilot Study. Antioxidants 2021, 10, 77. [Google Scholar] [CrossRef] [PubMed]
- Shimoda, R.; Nagashima, M.; Sakamoto, M.; Yamaguchi, N.; Hirohashi, S.; Yokota, J.; Kasai, H. Increased formation of oxidative DNA damage, 8-hydroxydeoxyguanosine, in human livers with chronic hepatitis. Cancer Res. 1994, 54, 3171–3172. [Google Scholar] [PubMed]
- Ma, N.; Liu, W.; Zhang, X.; Gao, X.; Yu, F.; Guo, W.; Meng, Y.; Gao, P.; Zhou, J.; Yuan, M.; et al. Oxidative Stress-Related Gene Polymorphisms Are Associated with Hepatitis B Virus-Induced Liver Disease in the Northern Chinese Han Population. Front. Genet. 2020, 10, 1290. [Google Scholar] [CrossRef] [PubMed]
- Popa, G.L.; Popa, M.I. Oxidative Stress in Chronic Hepatitis B—An Update. Microorganisms 2022, 10, 1265. [Google Scholar] [CrossRef] [PubMed]
- Stadtman, E.R.; Levine, R.L. Protein Oxidation. Ann. N. Y. Acad. Sci. 2000, 899, 191–208. [Google Scholar] [CrossRef]
- Zheng, P.; Dou, Y.; Wang, Q. Immune response and treatment targets of chronic hepatitis B virus infection: Innate and adaptive immunity. Front. Cell. Infect. Microbiol. 2023, 13, 1206720. [Google Scholar] [CrossRef]
- Liu, Y.; Hao, C.; Li, L.; Zhang, H.; Zha, W.; Ma, L.; Chen, L.; Gan, J. The Role of Oxidative Stress in the Development and Therapeutic Intervention of Hepatocellular Carcinoma. Curr. Cancer Drug Targets 2023, 23, 792–804. [Google Scholar] [CrossRef] [PubMed]
- Bolukbas, C.; Bolukbas, F.F.; Horoz, M.; Aslan, M.; Celik, H.; Erel, O. Increased oxidative stress associated with the severity of the liver disease in various forms of hepatitis B virus infection. BMC Infect. Dis. 2005, 5, 95. [Google Scholar] [CrossRef] [PubMed]
- Wang, H.; Huang, W.; Lai, M.; Su, I. Hepatitis B virus pre-S mutants, endoplasmic reticulum stress and hepatocarcinogenesis. Cancer Sci. 2006, 97, 683–688. [Google Scholar] [CrossRef]
- Unbbreen, A.N.; Hussain, S.; Syed, R.; Ali, W.; Khurshid, Q.; Hussain, M.; Rehman, A.I.; Afzal, J. Oxidative stress in the patients of hepatitis C virus. Oxid. Commun. 2016, 39, 1405–1416. [Google Scholar]
- Demirdag, K.; Yilmaz, S.; Ozdarendeli, A.; Ozden, M.; Kalkan, A.; Kilic, S.S. Levels of plasma malondialdehyde and erythrocyte antioxidant enzyme activities in patients with chronic hepatitis B. Hepatogastroenterology 2003, 50, 766–770. [Google Scholar] [PubMed]
- Boya, P.; de la Peña, A.; Beloqui, O.; Larrea, E.; Conchillo, M.; Castelruiz, Y.; Civeira, M.-P.; Prieto, J. Antioxidant status and glutathione metabolism in peripheral blood mononuclear cells from patients with chronic hepatitis C. J. Hepatol. 1999, 31, 808–814. [Google Scholar] [CrossRef]
- Romero, M.J.; Bosch-Morell, F.; Romero, B.; Rodrigo, J.M.; A Serra, M.; Romero, F.J. Serum malondialdehyde: Possible use for the clinical management of chronic hepatitis C patients. Free. Radic. Biol. Med. 1998, 25, 993–997. [Google Scholar] [CrossRef] [PubMed]
- Dikici, I.; Mehmetoglu, I.; Dikici, N.; Bitirgen, M.; Kurban, S. Investigation of oxidative stress and some antioxidants in patients with acute and chronic viral hepatitis B and the effect of interferon-α treatment. Clin. Biochem. 2005, 38, 1141–1144. [Google Scholar] [CrossRef] [PubMed]
- Levent, G.; Ali, A.; Ahmet, A.; Polat, E.C.; Aytaç, Ç.; Ayşe, E.; Ahmet, S. Oxidative stress and antioxidant defense in patients with chronic hepatitis C patients before and after pegylated interferon alfa-2b plus ribavirin therapy. J. Transl. Med. 2006, 4, 25. [Google Scholar] [CrossRef] [PubMed]
- Chrobot, A.M.; Szaflarska-Szczepanik, A.; Drewa, G. Antioxidant defense in children with chronic viral hepatitis B and C. Med. Sci. Monit. 2000, 6, 713–718. [Google Scholar]
- Nigam, M.; Mishra, A.P.; Deb, V.K.; Dimri, D.B.; Tiwari, V.; Bungau, S.G.; Bungau, A.F.; Radu, A.-F. Evaluation of the association of chronic inflammation and cancer: Insights and implications. Biomed. Pharmacother. 2023, 164, 115015. [Google Scholar] [CrossRef]
- Azoicai, A.N.; Stana, B.A. Oxidative Stress in Children Chronic Hepatitis. Romanian J. Pediatr. 2016, 66, 18–23. [Google Scholar] [CrossRef]
- Ivanov, A.V.; Valuev-Elliston, V.T.; Tyurina, D.A.; Ivanova, O.N.; Kochetkov, S.N.; Bartosch, B.; Isaguliants, M.G. Oxidative stress, a trigger of hepatitis C and B virus-induced liver carcinogenesis. Oncotarget 2016, 8, 3895–3932. [Google Scholar] [CrossRef] [PubMed]
- Okuda, M.; Li, K.; Beard, M.R.; Showalter, L.A.; Scholle, F.; Lemon, S.M.; Weinman, S.A. Mitochondrial injury, oxidative stress, and antioxidant gene expression are induced by hepatitis C virus core protein. Gastroenterology 2002, 122, 366–375. [Google Scholar] [CrossRef]
- Czuczejko, J.; Mila-Kierzenkowska, C.; Szewczyk-Golec, K. Plasmaα-GlutathioneS-Transferase Evaluation in Patients with Acute and Chronic Liver Injury. Can. J. Gastroenterol. Hepatol. 2019, 2019, 5850787. [Google Scholar] [CrossRef] [PubMed]
- Farias, M.S.; Budni, P.; Ribeiro, C.M.; Parisotto, E.B.; Santos, C.E.I.; Dias, J.F.; Dalmarco, E.M.; Fröde, T.S.; Pedrosa, R.C.; Filho, D.W. Antioxidant supplementation attenuates oxidative stress in chronic hepatitis C patients. Gastroenterol. Hepatol. 2012, 35, 386–394. [Google Scholar] [CrossRef] [PubMed]
- Kodama, H.; Fujisawa, C.; Bhadhprasit, W. Inherited copper transport disorders: Biochemical mechanisms, diagnosis, and treatment. Curr. Drug Metab. 2012, 13, 237–250. [Google Scholar] [CrossRef]
- Nagasaka, H.; Inoue, I.; Inui, A.; Komatsu, H.; Sogo, T.; Murayama, K.; Murakami, T.; Yorifuji, T.; Asayama, K.; Katayama, S.; et al. Relationship between oxidative stress and antioxidant systems in the liver of patients with wilson disease: Hepatic manifestation in wilson disease as a consequence of augmented oxidative stress. Pediatr. Res. 2006, 60, 472–477. [Google Scholar] [CrossRef] [PubMed]
- Tanzi, R.; Petrukhin, K.; Chernov, I.; Pellequer, J.; Wasco, W.; Ross, B.; Romano, D.; Parano, E.; Pavone, L.; Brzustowicz, L.; et al. The Wilson disease gene is a copper transporting ATPase with homology to the Menkes disease gene. Nat. Genet. 1993, 5, 344–350. [Google Scholar] [CrossRef] [PubMed]
- Linzay, C.D.; Sharma, B.; Pandit, S. Autoimmune Hepatitis. [Updated 2023 Aug 14]. In StatPearls [Internet]; StatPearls Publishing: Treasure Island, FL, USA, 2024; Available online: https://www.ncbi.nlm.nih.gov/books/NBK459186/ (accessed on 23 January 2024).
- Czaja, A.J. Epigenetic changes and their implications in autoimmune hepatitis. Eur. J. Clin. Investig. 2022, 52, e13793. [Google Scholar] [CrossRef] [PubMed]
- Wang, G.; Tanaka, A.; Zhao, H.; Jia, J.; Ma, X.; Harada, K.; Wang, F.-S.; Wei, L.; Wang, Q.; Sun, Y.; et al. The Asian Pacific Association for the Study of the Liver clinical practice guidance: The diagnosis and management of patients with autoimmune hepatitis. Hepatol. Int. 2021, 15, 223–257. [Google Scholar] [CrossRef]
- Tao, S.; Zhang, H.; Zhao, Q.; Bu, H.; Wang, H.; Guo, H. Correlation of vitamin D with inflammatory factors, oxidative stress and T cell subsets in patients with autoimmune hepatitis. Exp. Ther. Med. 2020, 19, 3419–3424. [Google Scholar] [CrossRef]
- Vaja, R.; Rana, M. Drugs and the liver. Anaesth. Intensiv. Care Med. 2020, 21, 517–523. [Google Scholar] [CrossRef]
- Rasool, M.K.; Sabina, E.P.; Ramya, S.R.; Preety, P.; Patel, S.; Mandal, N.; Mishra, P.P.; Samuel, J. Hepatoprotective and antioxidant effects of gallic acid in paracetamol-induced liver damage in mice. J. Pharm. Pharmacol. 2010, 62, 638–643. [Google Scholar] [CrossRef] [PubMed]
- Curcio, A.; Romano, A.; Cuozzo, S.; Di Nicola, A.; Grassi, O.; Schiaroli, D.; Nocera, G.F.; Pironti, M. Silymarin in Combination with Vitamin C, Vitamin E, Coenzyme Q10 and Selenomethionine to Improve Liver Enzymes and Blood Lipid Profile in NAFLD Patients. Medicina 2020, 56, 544. [Google Scholar] [CrossRef] [PubMed]
- Aghababaei, F.; Hadidi, M. Recent Advances in Potential Health Benefits of Quercetin. Pharmaceuticals 2023, 16, 1020. [Google Scholar] [CrossRef]
- Chaudhary, P.; Janmeda, P.; Docea, A.O.; Yeskaliyeva, B.; Razis, A.F.A.; Modu, B.; Calina, D.; Sharifi-Rad, J. Oxidative stress, free radicals and antioxidants: Potential crosstalk in the pathophysiology of human diseases. Front. Chem. 2023, 11, 1158198. [Google Scholar] [CrossRef] [PubMed]
- Tappel, A.L. Lipid peroxidation damage to cell components. Fed. Proc. 1973, 32, 1870–1874. [Google Scholar]
- Catal, T.; Bolkent, S. Combination of selenium and three naturally occurring antioxidants administration protects D-galactosamine-induced liver injury in rats. Biol. Trace Element Res. 2008, 122, 127–136. [Google Scholar] [CrossRef] [PubMed]
- Esrefoglu, M. Oxidative stress and benefits of antioxidant agents in acute and chronic hepatitis. Hepat. Mon. 2012, 12, 160–167. [Google Scholar] [CrossRef] [PubMed]
- Myhrstad, M.C.; Carlsen, H.; Nordström, O.; Blomhoff, R.; Moskaug, J. Flavonoids increase the intracellular glutathione level by transactivation of the gamma-glutamylcysteine synthetase catalytical subunit promoter. Free. Radic. Biol. Med. 2002, 32, 386–393. [Google Scholar] [CrossRef] [PubMed]
- Jia, J.-D.; Bauer, M.; Cho, J.J.; Ruehl, M.; Milani, S.; Boigk, G.; Riecken, E.O.; Schuppan, D. Antifibrotic effect of silymarin in rat secondary biliary fibrosis is mediated by downregulation of procollagen α1(I) and TIMP-1. J. Hepatol. 2001, 35, 392–398. [Google Scholar] [CrossRef]
- Sen, S.; Chakraborty, R. The role of antioxidants in human health. In Oxidative Stress: Diagnostics, Prevention, and Therapy; American Chemical Society: Washington, DC, USA, 2011. [Google Scholar]
- Ostrakhovitch, E.A.; Afanas’ev, I.B. Oxidative stress in rheumatoid arthritis leukocytes: Suppression by rutin and other antioxidants and chelators. Biochem. Pharmacol. 2001, 62, 743–746. [Google Scholar] [CrossRef]
- Stehbens, W.E. Oxidative stress in viral hepatitis and AIDS. Exp. Mol. Pathol. 2004, 77, 121–132. [Google Scholar] [CrossRef] [PubMed]
- Pár, A.; Rőth, E.; Miseta, A.; Hegedüs, G.; Pár, G.; Hunyady, B.; Vincze, A. Az antioxidáns flavonoid silymarin szupplementációja hatásának placebokontrollos vizsgálata PEG-IFN + ribavirin antivirális kezelésben részesülô krónikus C-hepatitises betegekben [Effects of supplementation with the antioxidant flavonoid, silymarin, in chronic hepatitis C patients treated with peg-interferon + ribavirin. A placebo-controlled double blind study]. Orvosi Hetil. 2009, 150, 73–79. [Google Scholar] [CrossRef]
- Koushki, M.; Yekta, R.F.; Amiri-Dashatan, N. Critical review of therapeutic potential of silymarin in cancer: A bioactive polyphenolic flavonoid. J. Funct. Foods 2023, 104, 105502. [Google Scholar] [CrossRef]
- Buzzelli, G.; Moscarella, S.; Giusti, A.; Duchini, A.; Marena, C.; Lampertico, M. A pilot study on the liver protective effect of si-lybin-phosphatidylcholine complex (IdB1016) in chronic active hepatitis. Int. J. Clin. Pharmacol. Ther. Toxicol. 1993, 31, 456–460. [Google Scholar] [PubMed]
- Liu, C.-H.; Jassey, A.; Hsu, H.-Y.; Lin, L.-T. Antiviral Activities of Silymarin and Derivatives. Molecules 2019, 24, 1552. [Google Scholar] [CrossRef]
- Zhang, C.-Y.; Liu, S.; Yang, M. Antioxidant and anti-inflammatory agents in chronic liver diseases: Molecular mechanisms and therapy. World J. Hepatol. 2023, 15, 180–200. [Google Scholar] [CrossRef]
- Shan, S.; Liu, Z.; Liu, Z.; Zhang, C.; Song, F. MitoQ alleviates carbon tetrachloride-induced liver fibrosis in mice through regulating JNK/YAP pathway. Toxicol. Res. 2022, 11, 852–862. [Google Scholar] [CrossRef]
- Wang, J.; Du, L.; Tang, H. Suppression of Interferon-α Treatment Response by Host Negative Factors in Hepatitis B Virus Infection. Front. Med. 2021, 8, 784172. [Google Scholar] [CrossRef]
- Ye, J.; Chen, J. Interferon and Hepatitis B: Current and Future Perspectives. Front. Immunol. 2021, 12, 733364. [Google Scholar] [CrossRef]
- Kozlov, E.M.; Ivanova, E.; Grechko, A.V.; Wu, W.-K.; Starodubova, A.V.; Orekhov, A.N. Involvement of Oxidative Stress and the Innate Immune System in SARS-CoV-2 Infection. Diseases 2021, 9, 17. [Google Scholar] [CrossRef]
- Pisoschi, A.M.; Pop, A.; Iordache, F.; Stanca, L.; Geicu, O.I.; Bilteanu, L.; Serban, A.I. Antioxidant, anti-inflammatory and immunomodulatory roles of vitamins in COVID-19 therapy. Eur. J. Med. Chem. 2022, 232, 114175. [Google Scholar] [CrossRef] [PubMed]
- Farbstein, D.; Kozak-Blickstein, A.; Levy, A.P. Antioxidant Vitamins and Their Use in Preventing Cardiovascular Disease. Molecules 2010, 15, 8098–8110. [Google Scholar] [CrossRef] [PubMed]
- Sinbad, O.O.; Folorunsho, A.A.; Olabisi, O.L.; Ayoola, O.A.; Temitope, E.J. Vitamins as Antioxidants. J. Food Sci. Nutr. Res. 2019, 2, 214–235. [Google Scholar]
- Petta, S.; Cammà, C.; Scazzone, C.; Tripodo, C.; Di Marco, V.; Bono, A.; Cabibi, D.; Licata, G.; Porcasi, R.; Marchesini, G.; et al. Low vitamin D serum level is related to severe fibrosis and low responsiveness to interferon-based therapy in genotype 1 chronic hepatitis C. J. Hepatol. 2010, 51, 1158–1167. [Google Scholar] [CrossRef] [PubMed]
- Arteh, J.; Narra, S.; Nair, S. Prevalence of vitamin D deficiency in chronic liver disease. Dig. Dis. Sci. 2009, 55, 2624–2628. [Google Scholar] [CrossRef] [PubMed]
- Hoan, N.X.; Van Tong, H.; Song, L.H.; Meyer, C.G.; Velavan, T.P. Vitamin D deficiency and hepatitis viruses-associated liver diseases: A literature review. World J. Gastroenterol. 2018, 24, 445–460. [Google Scholar] [CrossRef] [PubMed]
- Licata, A.; Zerbo, M.; Como, S.; Cammilleri, M.; Soresi, M.; Montalto, G.; Giannitrapani, L. The Role of Vitamin Deficiency in Liver Disease: To Supplement or Not Supplement? Nutrients 2021, 13, 4014. [Google Scholar] [CrossRef] [PubMed]
- Mrowicka, M.; Mrowicki, J.; Dragan, G.; Majsterek, I. The importance of thiamine (vitamin B1) in humans. Biosci. Rep. 2023, 43, BSR20230374. [Google Scholar] [CrossRef] [PubMed]
- Mehta, R.; Dedina, L.; O’brien, P.J. Rescuing hepatocytes from iron-catalyzed oxidative stress using vitamins B1 and B6. Toxicol. Vitr. 2011, 25, 1114–1122. [Google Scholar] [CrossRef]
- Plauth, M.; Bernal, W.; Dasarathy, S.; Merli, M.; Plank, L.D.; Schütz, T.; Bischoff, S.C. ESPEN guideline on clinical nutrition in liver disease. Clin. Nutr. 2019, 38, 485–521. [Google Scholar] [CrossRef]
- Lai, C.-L.; Lin, H.-J.; Yeoh, E.-K.; Lok, A.S.-F.; Wu, P.-C.; Yeung, C.-Y. Placebo-controlled trial of recombinant alpha 2-interferon in Chinese HBsAg-carrier children. Lancet 1987, 330, 877–880. [Google Scholar] [CrossRef] [PubMed]
- Lai, C.-L.; Lin, H.-J.; Lau, J.-N.; Flok, A.; Wu, P.-C.; Chung, H.-T.; Wong, L.-K.; Leung, M.; Yeung, C.-Y. Effect of recombinant alpha2 interferon with or without prednisone in Chinese HBsAg carrier children. Q. J. Med. 1991, 78, 155–163. [Google Scholar] [CrossRef] [PubMed]
- Wallace, A.E.; Weeks, W.B. Thiamine treatment of chronic hepatitis B infection. Am. J. Gastroenterol. 2001, 96, 864–868. [Google Scholar] [CrossRef] [PubMed]
- Sharifi-Rad, M.; Anil Kumar, N.V.; Zucca, P.; Varoni, E.M.; Dini, L.; Panzarini, E.; Rajkovic, J.; Tsouh Fokou, P.V.; Azzini, E.; Peluso, I.; et al. Lifestyle, Oxidative Stress, and Antioxidants: Back and Forth in the Pathophysiology of Chronic Diseases. Front. Physiol. 2020, 11, 694. [Google Scholar] [CrossRef]
- Ungurianu, A.; Zanfirescu, A.; Nițulescu, G.; Margină, D. Vitamin E beyond Its Antioxidant Label. Antioxidants 2021, 10, 634. [Google Scholar] [CrossRef] [PubMed]
- Alavian, S.M.; Showraki, A. Hepatitis B and its Relationship with Oxidative Stress. Hepat. Mon. 2016, 16, e37973. [Google Scholar] [CrossRef]
- Andreone, P.; Fiorino, S.; Cursaro, C.; Gramenzi, A.; Margotti, M.; Di Giammarino, L.; Biselli, M.; Miniero, R.; Gasbarrini, G.; Bernardi, M. Vitamin E as treatment for chronic hepatitis B: Results of a randomized controlled pilot trial. Antivir. Res. 2001, 49, 75–81. [Google Scholar] [CrossRef] [PubMed]
- Fiorino, S.; Bacchi-Reggiani, M.L.; Leandri, P.; Loggi, E.; Andreone, P. Vitamin E for the treatment of children with hepatitis B e antigen-positive chronic hepatitis: A systematic review and meta-analysis. World J. Hepatol. 2017, 9, 333–342. [Google Scholar] [CrossRef]
- Von Herbay, A.; Stahl, W.; Niederau, C.; Sies, H. Vitamin E improves the aminotransferase status of patients suffering from viral hepatitis C: A randomized, double-blind, placebo-controlled study. Free. Radic. Res. 1997, 27, 599–605. [Google Scholar] [CrossRef]
- Look, M.P.; Gerard, A.; Rao, G.S.; Sudhop, T.; Fischer, H.-P.; Sauerbruch, T.; Spengler, U. Interferon/antioxidant combination therapy for chronic hepatitis C—A controlled pilot trial. Antivir. Res. 1999, 43, 113–122. [Google Scholar] [CrossRef]
- Falasca, K.; Ucciferri, C.; Mancino, P.; Vitacolonna, E.; De Tullio, D.; Pizzigallo, E.; Conti, P.; Vecchiet, J. Treatment with silybin-vitamin E-phospholipid complex in patients with hepatitis C infection. J. Med. Virol. 2008, 80, 1900–1906. [Google Scholar] [CrossRef] [PubMed]
- Gerner, P.; Posselt, H.-G.; Krahl, A.; Ballauff, A.; Innerhofer, A.; Binder, C.; Wenzl, T.G.; Zense, M.; Hector, A.; Dockter, G.; et al. Vitamin E treatment for children with chronic hepatitis B: A randomized placebo controlled trial. World J. Gastroenterol. 2008, 14, 7208–7213. [Google Scholar] [CrossRef] [PubMed]
- Ideo, G.; Bellobuono, A.; Tempini, S.; Mondazzi, L.; Airoldi, A.; Benetti, G.; Bissoli, F.; Cestari, C.; Colombo, E.; Del Poggio, P.; et al. Antioxidant drugs combined with alpha-interferon in chronic hepatitis C not responsive to alpha-interferon alone: A randomized, multicentre study. Eur. J. Gastroenterol. Hepatol. 1999, 11, 1203–1207. [Google Scholar] [CrossRef] [PubMed]
- Morbitzer, M.; Herget, T. Expression of gastrointestinal glutathione peroxidase is inversely correlated to the presence of hepatitis C virus subgenomic RNA in human liver cells. J. Biol. Chem. 2005, 280, 8831–8841. [Google Scholar] [CrossRef] [PubMed]
- Böcher, W.O.; Wallasch, C.; Höhler, T.; Galle, P.R. All-trans retinoic acid for treatment of chronic hepatitis C. Liver Int. 2008, 28, 347–354. [Google Scholar] [CrossRef]
- Wang, M.-L.; Yin, X.-J.; Li, X.-L.; Wang, F.-D.; Zhou, J.; Tao, Y.-C.; Wang, Y.-H.; Wu, D.-B.; Chen, E.-Q. Retrospective Analysis of the Clinical Efficacy of N-Acetylcysteine in the Treatment of Hepatitis B Virus Related Acute-on-Chronic Liver Failure. Front. Med. 2021, 8, 724224. [Google Scholar] [CrossRef]
- Shohrati, M.; Dermanaki, F.; Babaei, F.; Alavian, S.M. Evaluation of the effects of oral N-acetylcysteine and a placebo in para-clinical and oxidative stress parameters of patients with chronic hepatitis B. Hepat Mon. 2010, 10, 95–100. [Google Scholar]
- Fan, Y.C.; Wang, K.; Han, L.Y.; Li, X.H.; Wang, H.M.; Wang, L.Y.; Hou, Y.D. Oxidative stress in patients with chronic hepatitis B before and after interferon alpha-2b treatment. Zhonghua Shi Yan He Lin Chuang Bing Du Xue Za Zhi = Chin. J. Exp. Clin. Virol. 2007, 21, 23–25. [Google Scholar]
- Kaźmierczak-Barańska, J.; Boguszewska, K.; Adamus-Grabicka, A.; Karwowski, B.T. Two Faces of Vitamin C—Antioxidative and Pro-Oxidative Agent. Nutrients 2020, 12, 1501. [Google Scholar] [CrossRef]
- Blot, W.J.; Li, J.-Y.; Taylor, P.R.; Guo, W.; Dawsey, S.; Wang, G.-Q.; Yang, C.S.; Zheng, S.-F.; Gail, M.; Li, G.-Y.; et al. Nutrition intervention trials in Linxian, China: Supplementation with specific vitamin/mineral combinations, cancer incidence, and disease-specific mortality in the general population. J. Natl. Cancer Inst. 1993, 85, 1483–1491. [Google Scholar] [CrossRef]
- Slagle, B.L.; Bouchard, M.J. Hepatitis B Virus X and Regulation of Viral Gene Expression. Cold Spring Harb. Perspect. Med. 2016, 6, a021402. [Google Scholar] [CrossRef]
Authors | Patients | MDA Levels | GSH Levels | SOD Levels | CAT Levels |
---|---|---|---|---|---|
N Aslam et al. [57] | 36 patients:
| ↑ | ↓ | ↓ | - |
P Cıragil et al. [22] | 70 patients:
| ↑ | - | ↓↓ CHC ↓ CHB | ↓ |
I Dikici et al. [61] | 71 patients:
| ↑ | ↓ | - | - |
G Levent et al. [62] | 47 patients:
| ↑ | ↓ | ↓ | - |
AM Chrobot et al. [63] | 100 patients with CHC | ↑ | ↓ | ↓ | ↓ |
Antioxidants Used as Adjuvant Treatment in Chronic Hepatitis: | Effects: |
---|---|
Vitamin E (alpha-tocopherol) | Together with alpha-tocopherol, selenium, ascorbic acid, beta carotene, and ubiquinone, slowed down the liver damage caused by D-galactosamine [82,83]. Sustains the cell antioxidant defense system [112,113,114,115]. Has antioxidant activity, by neutralizing ROS and free radicals [112,113]. Has an important role in immunomodulation, influencing cell-mediated immunity [115]. Could contribute to ALT normalization and to decreasing of HBV-DNA viremia [115]. |
Vitamin A, vitamin C, flavonoids, and phenolic compounds | Sustains the cell antioxidant defense system [85,86,87]. |
Selenium | Can act on hydrogen peroxide free radicals and repair damaged sites [79]. |
Vitamin D2 | Potential adjuvant for interferon therapy because it can reduce HCV activity in hepatocytes [84]. |
Beta-carotene | Potential adjuvant for interferon therapy because it can reduce HCV activity in hepatocytes [84]. |
Silymarin | Reduces oxidative stress alone [88,89,90] Significantly improved the cell survival [91,92]. Has antiviral action, reducing hepatitis C virus replication [93]. |
Quercetin | It has the capacity to reduce viral extension and viral protein production in a tissue culture [94]. |
Disclaimer/Publisher’s Note: The statements, opinions and data contained in all publications are solely those of the individual author(s) and contributor(s) and not of MDPI and/or the editor(s). MDPI and/or the editor(s) disclaim responsibility for any injury to people or property resulting from any ideas, methods, instructions or products referred to in the content. |
© 2024 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/).
Share and Cite
Ioniuc, I.; Lupu, A.; Tarnita, I.; Mastaleru, A.; Trandafir, L.M.; Lupu, V.V.; Starcea, I.M.; Alecsa, M.; Morariu, I.D.; Salaru, D.L.; et al. Insights into the Management of Chronic Hepatitis in Children—From Oxidative Stress to Antioxidant Therapy. Int. J. Mol. Sci. 2024, 25, 3908. https://doi.org/10.3390/ijms25073908
Ioniuc I, Lupu A, Tarnita I, Mastaleru A, Trandafir LM, Lupu VV, Starcea IM, Alecsa M, Morariu ID, Salaru DL, et al. Insights into the Management of Chronic Hepatitis in Children—From Oxidative Stress to Antioxidant Therapy. International Journal of Molecular Sciences. 2024; 25(7):3908. https://doi.org/10.3390/ijms25073908
Chicago/Turabian StyleIoniuc, Ileana, Ancuta Lupu, Irina Tarnita, Alexandra Mastaleru, Laura Mihaela Trandafir, Vasile Valeriu Lupu, Iuliana Magdalena Starcea, Mirabela Alecsa, Ionela Daniela Morariu, Delia Lidia Salaru, and et al. 2024. "Insights into the Management of Chronic Hepatitis in Children—From Oxidative Stress to Antioxidant Therapy" International Journal of Molecular Sciences 25, no. 7: 3908. https://doi.org/10.3390/ijms25073908